̽��ֱ�� of Cambridge - personalised medicine

Ambitious goals for Dawn – the UK's fastest AI supercomputer

lw355 — Fri, 23 Feb 2024 06:30:12 +0000

Dawn is now being deployed for use by scientists within Cambridge and across the UK to support ambitious goals in clean energy, personalised medicine and climate.

̽��ֱ��women helping to change the story of ovarian cancer

lw355 — Mon, 24 Jan 2022 13:40:02 +0000

Every patient with cancer has a story to tell of their journey through diagnosis and treatment. We meet a group of women who are at the centre of pioneering research in Cambridge that’s changing the outcome of ovarian cancer – helping to create treatments that are as unique as their stories.

Take your medicine: how research into supply chains will help you take care of yourself

lw355 — Wed, 14 Jun 2017 15:20:27 +0000

“Like many people of my age, I have to take pills morning and night. I’m pretty good at taking them in the evenings, mainly because my wife makes me! But, left to my own devices in the mornings, I only remember to take them perhaps one day out of four,” says Dr Jag Srai.

“Wouldn’t it be fantastic if smartphones could remind patients, capture use and track activity, blood pressure, sugar level, and so on? And if, at the same time, their GP could see this data and call them in if there’s a problem?”

He explains that upwards of 30% of prescribed drugs are not taken by patients and, in the case of respiratory drugs, where application is more intricate, 70% are not taken as directed. ̽��ֱ��numbers vary depending on the type of condition being treated but they are disarmingly high across the board. This has consequences, and not only for the patient. ̽��ֱ��cost to the taxpayer of drugs that are not being used is considerable and reduces the pot of money available for patient care.

“In a world of scarce resources this in itself seems incredibly wasteful. But there are other reasons to be concerned,” adds Srai, who is Head of the Institute for Manufacturing (IfM)’s Centre for International Manufacturing. “Around 50% of patients taking antibiotics don’t complete the course. ̽��ֱ��consequences of this are potentially catastrophic as infections become increasingly resistant to drug treatment. And drugs contain active ingredients which, when disposed of inappropriately, end up as contaminants in our water supply.”

Tackling the thorny problem of patient compliance is just one aspect of the pharmaceutical industry that Srai and his team at the IfM are looking to revolutionise. They are working with other universities and major UK pharmaceutical companies AstraZeneca and GSK to make improvements across the whole supply chain, from how a pill is made to the moment it’s swallowed by the patient.

Advances in genetics and biochemistry are helping us move towards a much more tailored approach to medicine, focused on more targeted or niche patient populations, and ultimately the development of bespoke treatments to meet individual patient needs. ̽��ֱ��implications for how the pharmaceutical industry manufactures its medicines and gets them to the patient are clearly immense.

Most pharmaceutical manufacturing still takes place in huge factory complexes, where large volumes of chemicals are processed in a series of ‘batch-processing’ steps, and often a dozen or more are required to produce the final oral dose tablet. Developing new drugs is an expensive business and so big pharma companies hope for a ‘blockbuster’ drug – a medicine that could be used to treat a very common condition, such as asthma or high blood pressure, and which can be manufactured in large quantities.

But, says Srai, the manufacture of these blockbuster drugs is becoming a thing of the past. ̽��ֱ��batch process is costly, inefficient and makes less sense when producing medicines in small volumes.

New ‘continuous’ manufacturing processes mean that drugs can be made in a more flow-through model, requiring fewer steps in the manufacturing process, and in volumes better aligned with market demand. In the case of small volume manufacture, this technology breakthrough can support the move towards more personalised medicine.

“Combine this with the way in which digital technologies are transforming supply chains – through flexible production and automation, using sensors to track location, quality and authenticity, and big data analytics on consumption patterns – and it’s clear that the pharmaceutical industry is on the cusp of a huge change,” adds Srai.

Recognising this, and to make sure they harness the value these advances in science and technology can deliver, pharmaceutical companies are working together in a number of ‘pre-competitive forums’.

̽��ֱ��IfM team is playing a key part in two major related UK initiatives: the Continuous Manufacturing and Crystallisation (CMAC) Future Manufacturing Research Hub based at Strathclyde ̽��ֱ��, funded by £10m from the Engineering and Physical Sciences Research Council and a further £31m from industry; and REMEDIES, a £23m UK pharmaceutical supply-chain sector project, jointly funded by government and industry.

CMAC is focused on the move to continuous manufacturing and REMEDIES on developing new clinical and commercial supply chains. Srai’s team is leading the work on mapping the existing supply chains for different types of treatment, and modelling what the future might look like.

“We can envisage a future in which for some medicines, production is no longer a highly centralised large-scale batch operation but one where manufacturing is more about continuous processing, more distributed in nature, smaller scale and closer to the point of consumption.”

Asked how local this can become, Srai adds: “In some instances we are already able to ‘print’ tablet medicines on demand, and we are now exploring whether this might take place at more local production/distribution sites, or at the local pharmacy or even in our own homes. Of course, some critical hurdles still need to be overcome, not least in terms of assuring product quality at multiple sites and establishing appropriate regulatory regimes.

“New technologies are also opening up other possibilities in the way that patients receive healthcare. Wearable and smartphone apps could be feeding diagnostic and health information to our doctors – be they human or (with the advances in artificial intelligence) robot – who would assess our symptoms remotely. We may change our consultation habits completely and only go to the doctor for very specific types of treatment. Indeed, in the UK today, trials suggest some 30% of GP visits are unnecessary.”

As part of the REMEDIES project, the IfM team has been exploring the possibilities presented by technologies that are available now such as Quick Response (QR) codes that can be scanned by mobile apps on our smart phones – and how they can help ensure that patients are taking their medicine.

“A relatively easy thing to do with packaging is to use it as an information source for patients. For example, packs of pills come with a small leaflet that hardly anybody reads. If we want to help patients adhere to their treatment regimes, can we support them by giving them this plus more useful information in a more accessible electronic format?”

̽��ֱ��REMEDIES team is working on a mobile phone app that will allow patients to read the instructions on their phone (in a font size and language of their choice) or listen to some explanatory audio or watch a video. “This is simple, readily available technology that could have a significant impact on compliance,” says Srai.

̽��ֱ��potential for exploiting data to deliver bespoke healthcare in the future is enormous. With smart packaging, smartphones and wearable devices, information can become increasingly dynamic and interactive. Indicators such as time, location – even mood – can affect whether and how drugs are taken; and data such as blood pressure and pulse can show the effect they have on the patient.

“As in the world of e-commerce, we are at the early stages of understanding how this consumer and patient data can inform the supply chain,” says Srai. “But we can now contemplate scenarios in certain therapeutic areas, in which each dose a patient takes is fully optimised for the here and now, and manufactured continuously, or even printed on demand.”

And if the patient forgets to take it, they will, if they choose, be reminded to do so by a very insistent app.

Inset image: Read more about research on future therapeutics in Research Horizons magazine.

Researchers are working with pharmaceutical companies to make improvements across the whole supply chain, from how a pill is made to the moment it is swallowed by the patient.

We are already able to ‘print’ tablet medicines on demand, and we are now exploring whether this might take place at more local sites, or at the local pharmacy or even in our own homes.

Jag Srai

Kate Russell

Keep taking the tablets

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Future therapeutics: the hundred-year horizon scan

lw355 — Tue, 13 Jun 2017 08:04:43 +0000

It used to be all about fleabane for bites from venomous beasts, mugwort to induce and ease the pain of labour and boiled bedstraw to stimulate clotting. According to Nicholas Culpeper in his 1652 book ̽��ֱ��English Physitian, “a man may preserve his Body in Health; or cure himself, being sick, for three pence charge, with such things only as grow in England”.

Prescient words, in some respects – today it’s still all about giving the right patient the right drug, at the right dose at the right time, but it’s called precision medicine.

In fact, herbal remedies and small-molecule pharmaceuticals have dominated therapeutic medicines since Culpeper’s time, before being joined in the 1980s by ‘biologics’ when it became possible to build new forms of proteins, hormones, receptors and monoclonal antibodies after the DNA code was cracked in Cambridge in 1953.

Science moves fast and we now stand at the threshold of not one but several step changes. New understanding of the structures of cells and systems biology is pioneering the use of human and microbial cells as therapeutic agents. Meanwhile, novel bioelectronic medicines or ‘electroceuticals’ are shifting the therapeutic approach away from traditional medicines into optics, electronics, instrumentation and software. What will these and other developments in areas such as immunotherapy and nanotherapy mean to medicine over the next hundred years? And what’s taking place now in Cambridge to help this happen?

There seems little doubt that with increased genetic knowledge, precision medicine will define the 21st century. ̽��ֱ��development of massively parallel DNA sequencing by the Department of Chemistry moves us closer to the prospect of sequencing one billion kilobases per day per machine. Genomic information and computational approaches will refine diagnoses, stratify cancer into subtypes, guide personalised treatments and improve the efficiency of clinical trials.

Meanwhile, cell-based technologies provide exquisitely selective delivery agents that are naturally able to perform therapeutic tasks. In Cambridge, progress in regenerative medicine promises benefits for replacing human cells, tissues or organs; and the use of stem cells to manage and treat diabetes, degenerative nerve, bone and joint conditions, and heart failure.

̽��ֱ��convergence of information technologies like augmented reality, cloud-based applications, artificial intelligence and deep learning in digital healthcare will play an increasing role in medical decision support, robotic nursing and surgery, sensors and diagnostics, and so on.

So-called beyond-the-pill services, such as wearables, apps, medical tattoos and point-of-care sensors will offer consumers digital devices for monitoring health and compliance, although issues such as privacy, data integrity and cybersecurity remain concerns to be resolved satisfactorily in the ‘internet of people’.

Research into these key future technologies is being conducted in the Departments of Engineering, Materials Science and Physics, and the Centre for the Physics of Medicine. Meanwhile, the newly established Alan Turing Institute and the Leverhulme Centre for the Future of Intelligence bring world-leading expertise in big data, computer science, advanced mathematics and artificial intelligence.

How is the pharmaceutical industry responding to these shifting patterns in modern medical treatments? Global research-based companies have suffered from the downturn in the global economy, the demise of the blockbuster era and the rise in specialist markets. Industry is adapting by placing more emphasis on new therapeutic modalities and repurposing existing drugs, as well as strengthening academic–pharma collaborations at earlier stages of the drug discovery process.

̽��ֱ��Milner Therapeutics Institute, due to open in 2018, will foster close collaborative interactions between academia and industry to accelerate medical advancement via an ‘open borders’ paradigm. So too will Apollo Therapeutics, a £40m collaboration between the tech transfer offices of Cambridge, Imperial College London and ̽��ֱ�� College London and three global pharmaceutical industries (AstraZeneca, GSK and Johnson & Johnson) to streamline the academia-to-industry pipeline.

New technologies are likely to change the regulatory, legal and policy environments, and business models. For example, some forms of medicine – like gene editing – are both personalised and curative. How will the costs of research, development and marketing for ‘cures’ be met if the business model is more likely to be a service than a product?

Understanding complex issues such as these will be aided by the networks and convening power established by the Centre for Science and Policy, which coordinates the best scientific thinking to inform public policy, and the Centre for Law, Medicine and Life Sciences, which focuses on the legal and ethical challenges at the forefront of biomedicine. Meanwhile, the Institute for Manufacturing is analysing supply chains, and the Judge Business School is studying the management of innovation and entrepreneurship.

It’s likely that future healthcare will have a different geometry. A complex interplay of patients, industries and service operators will use sophisticated diagnostic tools, digital scrutiny and interpretation using artificial intelligence, and have access to an extensive toolbox of therapeutic approaches, all personalised to the individual patient, and available through a redesigned primary and hospital healthcare environment.

Cambridge is well placed to drive innovation in this highly multidisciplinary therapeutic scenario.

̽��ֱ�� ̽��ֱ�� has expertise relevant to all stages of the drug discovery, development and manufacturing process, from fundamental biology/chemistry, through drug development and clinical trials, to imaging, safety, delivery, supply-chain management and entrepreneurship.

There’s also large-scale investment in research and infrastructure for tackling disease. Take dementia, for instance: more than £17m awarded by the UK Research Partnership Investment Fund will help build a Chemistry of Health building for chemistry-based research in neurodegenerative diseases. Cambridge also hosts one of three UK Drug Discovery Institutes funded by Alzheimer’s Research UK (ARUK), and is one of five centres that will form the UK Dementia Research Institute, funded by the Medical Research Council, Alzheimer’s Society and ARUK.

Against this backdrop of activity, the Cambridge Academy of Therapeutic Sciences (CATS) has been established to increase the linking of academic research to big pharma, biotech and NHS structures on the Cambridge Biomedical Campus and in the region. ̽��ֱ��idea is to create a networking, training and enterprise structure that transcends traditional boundaries between clinicians, academics and industrialists, in which fundamental and applied research into diagnostics and therapeutics can flourish and be translated into patient treatments with maximum efficiency.

̽��ֱ��time is ripe for this to happen. AstraZeneca’s move to Cambridge, combined with close links with GSK and other big pharma companies, as well as the thriving local biotechnology industrial environment and sister institutes like the Wellcome Trust Sanger Institute, provide substantial impetus to co-develop and co-deliver these programmes.

In fact, one might thank Nicholas Culpeper for his vision for the future of medicine and at the same time upgrade his estimate of ‘three pence charge’ with 36 decades of financial inflation.

Inset image: Read more about research on future therapeutics in Research Horizons magazine.

How will precision medicine define 21st-century therapeutics? What will future healthcare look like? And what actually lies ‘beyond the pill’? Professor Chris Lowe, inaugural Director of the Cambridge Academy of Therapeutic Sciences, takes the long view on the future of therapeutics.

Future healthcare will have a different geometry... sophisticated diagnostic tools, cloud-based applications, artificial intelligence... an extensive toolbox of therapeutic approaches, all personalised to the individual.

Chris Lowe

̽��ֱ��District

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How bright is your digital future?

Anonymous — Wed, 18 Jan 2017 08:35:54 +0000

̽��ֱ��combination of new technologies, IT infrastructures and data analytics holds out an alluring possibility of a world in which the end-to-end supply chain is utterly transformed – highly connected, flexible, efficient, resilient and truly responsive to customer needs. Each of those attributes sounds attractively incremental but put them together and you have a completely new way of doing business and one in which customers are not just on the receiving end of a product or service but are central to it.

A good example of this is the pharmaceutical sector. As part of the REMEDIES project, we are working with the major players in the UK pharmaceutical supply chain to address some of the challenges they face, such as tackling the hundreds of days’ of inventory sitting in the supply chain and the vast quantities of waste caused by patients not taking the drugs they are prescribed.

Using digital technologies and data-rich systems to make the pharmaceutical supply chain much more efficient is one thing but we are also mapping an entirely new business model in which drugs can be manufactured to order – possibly at the local pharmacy. Not only would this meet a patient’s individual medical needs, but the consumption and effects of those drugs can be continuously monitored to help doctors better support their patients.

A brave new world, in other words, of personalised medicine enabled by digital manufacturing processes, digital infrastructures and lots of data. But realising this vision of a digital future remains elusive, particularly for the largest global businesses.

Many of these companies recognise the need to digitalise aspects of their supply chain, often in response to particular challenges. They may, for example, as in the pharmaceutical sector, have a pressing need to solve the intransigent inventory management issues that bedevil many supply chains. They may have an issue with quality and see digitalisation as the best way to ensure their products are of a consistently high quality and their provenance is traceable.

Or they may be losing competitive advantage through poor customer service and see a digital agenda as a way of regaining market share, possibly while supporting their ambitions to reduce environmental impact.

But developing an end-to-end digital supply chain involves a major transformation both at a conceptual level and in execution. And while thought leaders and change agents within big companies may see the prize, CEOs and shareholders will be much more cautious given the levels of investment and organisation-wide disruption it entails. This is particularly the case for the global giants with a history of merger and acquisition (M&A) and an array of legacy systems to integrate. Even without the complication of M&A, all large companies have to organise themselves into manageable structures, which have a natural tendency to turn into silos and hence become obstacles to organisational change.

There is also the wider question of a lack of digital skills and attitudes across the board – at senior and middle management levels as well as within day-to-day factory operations. Companies may be able to see the opportunity, acquire the technology and capture the data but a shortage of both skills and mindset presents a significant barrier.

One of the challenges with the digital supply chain vision is the sheer scale and ambition of it. At the Centre for International Manufacturing, we have begun to conceptualise what a digital supply chain might look like and break it down into key areas to help companies understand the key ways in which digitalisation can impact on their organisation. We have been doing this by talking to companies both individually and as a non-competitive group.

Having identified the key areas, we have been developing ‘maturity models’ against which companies can benchmark their current performance, identify where the greatest opportunities lie and start to think about where to prioritise their efforts.

Factory design and production processes

Digital developments in factory design and production processes underpin the extended supply chain. ̽��ֱ��flexible factory is an important concept in this rapidly moving environment: how can you design and configure a factory for technologies which you don’t yet know? In this context, factories need to be modular and reconfigurable. One of the questions our framework helps companies consider is this: it is relatively straightforward to design a state-of-the-art, highly flexible plug-and-play factory – but is it cost-effective? Is it where companies will be able to create and capture most value?

Making the most of data

Some companies are already very good at gathering product and customer data but the challenge is how to integrate that data and use it to make better decisions about, for example, product lifecycle management, sales forecasting and designing products and services in response to customer needs. Data ownership is fast becoming an important issue in the supply chain and service delivery context. When partners are involved, who owns and can access the data is a critical question. Data sharing and connectivity also raises the question of open source versus ‘black box’ and developing common international data standards across sectors. In this area we must also consider the resilience of these digital supply chains and understand the cyber security challenges they may present.

Flexibility versus connectivity

One of the conceptual and practical challenges for organisations is whether to build monolithic, enterprise-wide systems that can connect supply chains. Clearly, for many companies – particularly those with a history of M&A – it would require a huge act of organisational will, not to mention significant investment, to move to a common platform. And, would doing so actually deliver a sufficiently flexible and reconfigurable solution? Instead, companies are talking about developing a ‘digital backbone’ that can interface with other systems to provide more networked and flexible approaches to optimising the end-to-end supply chain. And this digital backbone is more than an IT system – it should embody the critical touch points and interfaces between organisations as well as the data architectures and analytics. It also signifies a cultural shift to digital.

̽��ֱ��last leg

Using web-based systems to fulfil orders and manage the complexity of last-mile logistics is something that we have seen business-to-consumer companies do with impressive levels of sophistication and achieve corresponding levels of competitive advantage. For many large manufacturers there is still work to be done in developing systems that can support product delivery to multiple points of sale and ultimately direct to the end customer. But the opportunities are clear and create a virtuous circle. By delivering better customer service you not only attract new customers (and retain the old ones) but you also get access to better customer data which in turn can improve both the product and the service you offer. There are also many efficiencies to be had from digitalising this last leg of the supply chain though better stock management and reduced transport costs.

Towards the digital supply chain

By breaking down the digital supply chain into distinct but connected scenarios against which companies can measure their performance and aspirations, we believe we have created a powerful framework that will help them develop their digital supply chain capabilities. ̽��ֱ��scenarios help to clarify thinking and develop a strategic approach to digitalisation which is both deliverable and will create maximum value for the company.

̽��ֱ��next step is to put the strategy into action.

First published in IfM Review.

Dr Jag Srai, Head of the Centre for International Manufacturing at Cambridge's Institute for Manufacturing, and colleagues are developing new ways to help companies embrace the challenges and opportunities of digitalising the extended supply chain. Here, he provides a glimpse of this digital future.

A brave new world of personalised medicine enabled by digital manufacturing processes, digital infrastructures and lots of data

Jag Srai

Jacqueline ter Haar

pharmaceuticals

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Teaching old cells new tricks

lw355 — Tue, 24 Apr 2012 14:41:44 +0000

How do you study a human disease that has no equivalent in animals and where the human cells in question are so hard to grow outside the body they cannot be tested in the laboratory? ̽��ֱ��answer, until now, was with great difficulty. But by using a new stem cell technique, that is set to change.

Dr Ludovic Vallier, who holds an MRC Senior Fellowship in the Anne McLaren Laboratory for Regenerative Medicine, Department of Surgery at Cambridge in collaboration with Professor David Lomas (Cambridge Institute for Medical Research and Department of Medicine), works on a group of devastating genetic diseases affecting the liver.

“We target metabolic diseases of the liver, diseases such as alpha 1 antitrypsin deficiency. It’s one of the most common single genetic disorders and the protein it affects – which is only produced by the liver – is really important because it controls activity of elastase in the lung. Without this control, people develop serious lung problems and the disease also affects the liver, so these patients develop liver failure,” he explained.

̽��ֱ��problem is that these diseases cannot be studied in vitro – in a dish – in the laboratory, he said: “You can’t take cells from the liver of these very sick patients, and if you could they wouldn’t grow, which means you don’t have any way of screening drugs that could help treat these diseases.”

Without effective drugs, the only current treatment is a liver transplant. “There is a huge shortage of organs and transplantation involves taking immunosuppressive drugs, which is heavy treatment especially in already fragile patients,” Dr Vallier said. “And the disease is progressive so it’s very complicated to manage.” Understandably, Dr Vallier is excited that a new method of producing stem cells developed in Japan has given him and other researchers a way of studying these diseases and screening potential drugs to treat them.

“ ̽��ֱ��new technology consists of taking cells from skin and reprogramming them so that they become stem cells – cells that are capable of proliferating and differentiating into almost all tissue types,” he said.

This reprogramming means a cell with a previously fixed identity can be taught a new one – in this case taking skin cells and reprogramming them to become liver cells. When the skin cells come from a patient with liver disease, these skin-turned-liver cells also have the disease, making them ideal for studying the disease and screening potential drugs to treat it.

According to Dr Vallier: “Because we can generate liver cells that mimic the disease of the original patient in vitro, that allows us to do basic studies that were impossible by biopsy or primary culture and also to do drug screening.” And because the skin cells can come from a whole range of people, it gives researchers access to a broad diversity of patients as well as overcoming some of the ethical concerns associated with embryonic stem cells.

“That’s a very important step because it solves the problems associated with a limited stock of stem cells,” he said, “and because it’s a simple method, it’s easily accessible to a wide number of laboratories.”

Showing this can be done in a small number of liver patients in Cambridge is an important proof of concept, and supports the possibility that a similar approach might be applicable to a wide range of other serious diseases that still lack effective treatments, including neurodegenerative diseases such as Parkinson’s and Alzheimer’s Disease as well as heart diseases.

And Cambridge – which now has almost 30 groups doing stem cell research and strong links between academic researchers and clinicians – is perfectly positioned to make the most of this new technique.

“ ̽��ֱ��Laboratory for Regenerative Medicine is starting to become an expert in this disease modelling and we are all part of a larger consortium, the Cambridge Stem Cell Initiative (SCI),” said Dr Vallier. “Together, we are putting together resources and scientific interest to really develop stem cells and their clinical application. ̽��ֱ��SCI is a unique consortium because it brings together a wealth of complementary expertise.”

While this first revolution involves in vitro disease modelling and drug screening, Dr Vallier hopes this work will ultimately lead to personalised cell-based therapies where liver cells reprogrammed from a patient’s own skin cells could be used in place of a liver transplant. “It will take time for us to assess this clinical use and show that it is safe as well as effective,” he explained, “but if you ask me again in five years I should be able to tell you whether we are going to do it.”

Much hyped by the media, stem cells have tremendous power to improve human health. As part of the Cambridge Stem Cell Initiative, Dr Ludovic Vallier’s research in the Anne McLaren Laboratory for Regenerative Medicine shows how stem cells can further our understanding of disease and help deliver much-needed new treatments.

̽��ֱ��new technology consists of taking cells from skin and reprogramming them so that they become stem cells – cells that are capable of proliferating and differentiating into almost all tissue types.

Dr Ludovic Vallier

Candy Cho

Stem cells

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